spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 21 January 2004
doi: 10.1242/dev.00961

Development 131, 943-951 (2004)
Published by The Company of Biologists 2004
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.00961v1
131/4/943    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Busch-Nentwich, E.
Right arrow Articles by Nicolson, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Busch-Nentwich, E.
Right arrow Articles by Nicolson, T.

The deafness gene dfna5 is crucial for ugdh expression and HA production in the developing ear in zebrafish

Elisabeth Busch-Nentwich1, Christian Söllner1, Henry Roehl2 and Teresa Nicolson3,*

1 Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany
2 Centre for Developmental Genetics, Department of Biomedical Science, University of Sheffield, Firth Court, Sheffield S10 2TN, UK
3 Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, OR 97201, USA

* Author for correspondence (e-mail: nicolson{at}ohsu.edu)

Accepted 30 October 2003

Over 30 genes responsible for human hereditary hearing loss have been identified during the last 10 years. The proteins encoded by these genes play roles in a diverse set of cellular functions ranging from transcriptional regulation to K+ recycling. In a few cases, the genes are novel and do not give much insight into the cellular or molecular cause for the hearing loss. Among these poorly understood deafness genes is DFNA5. How the truncation of the encoded protein DFNA5 leads to an autosomal dominant form of hearing loss is not clear. In order to understand the biological role of Dfna5, we took a reversegenetic approach in zebrafish. Here we show that morpholino antisense nucleotide knock-down of dfna5 function in zebrafish leads to disorganization of the developing semicircular canals and reduction of pharyngeal cartilage. This phenotype closely resembles previously isolated zebrafish craniofacial mutants including the mutant jekyll. jekyll encodes Ugdh [uridine 5'-diphosphate (UDP)-glucose dehydrogenase], an enzyme that is crucial for production of the extracellular matrix component hyaluronic acid (HA). In dfna5 morphants, expression of ugdh is absent in the developing ear and pharyngeal arches, and HA levels are strongly reduced in the outgrowing protrusions of the developing semicircular canals. Previous studies suggest that HA is essential for differentiating cartilage and directed outgrowth of the epithelial protrusions in the developing ear. We hypothesize that the reduction of HA production leads to uncoordinated outgrowth of the canal columns and impaired facial cartilage differentiation.

Key words: dfna5, Deafness, Zebrafish, Semicircular canals, Pharyngeal cartilage, UDP-glucose dehydrogenase, Hyaluronic acid






© The Company of Biologists Ltd 2004